OE L27 Regulation of Salivary Flow Flashcards
Provide an overview of salivary flow regulation.
- GPCRs are found in the cell membrane of acinar cells
- Ligands (soluble molecules derived from the CNS) are sensed by GPCRs
- Binding causes downstream signalling events which result in increased or decreased salivary flow
What are the major contents of serous secretions?
- Glycoproteins
- Amylase
- Water
- Ions (bicarbonate to regulate pH)
What are the major contents of mucous secretions?
- Mucins
- Protective proteins
Outline the process of GPCR activation.
- Ligand binds to the extracellular side of the GPCR
- Changes arrangement of transmembrane helices
- On the intracellular surface this causes the connecting loops between helices to change shape to allow binding of G proteins
- GDP-GTP exchange activates secondary messenger systems
Describe the events of GPCR activation in more depth.
- The GPCR changes shape on the intracellular surface
- Allows G-alpha subunit of the G-protein to interact with activated GPCR
- Causes exchange of GDP with GTP
- GTP activates and interacts with effector molecules
- G-alpha unit dissociated and GPCR returns to inactive state
What type of innervation stimulates serous vs mucous secretion?
Serous: parasympathetic
Mucous: sympathetic
What is the GPCR (and its ligand) involved in parasympathetic secretion?
- Muscarinic acetylcholine receptor
Ligand = acetylcholine
Describe parasympathetic stimulation of serous acini for serous saliva secretion.
- Acetylcholine binds to the muscarinic acetylcholine receptor
- Causes a calcium flux
- Calcium triggers activation of potassium and chloride channels, and aquaporin channels
- Chloride and sodium ions released into duct lumen, AQP5 channels opened, amylase released from secretory vesicles
What are cholinergic drugs?
- Stimulate muscarinic acetylcholine receptors
- Increases salivary flow
E.g. pilocarpine
What are anti-cholinergic drugs?
- Inhibits the M3 muscarinic receptor
- Reduces salivary flow
- Used in tricyclic antidepressants, Parkinson disease medication and antihistamines
What is the GPCR (and its ligand) involved in sympathetic secretion?
- Beta-adrenergic receptor
Ligand = noradrenaline
Describe sympathetic stimulation of mucous acini for mucous secretion.
- Noradrenaline binds to beta-adrenergic receptor
- Activates adenylate cyclase which converts ATP to cAMP
- Secondary messenger cAMP
- cAMP activates protein kinase A
- PKA phosphorylates target proteins in the cytosol, they move to the nucleus and induce synthesis of subsequent proteins
What are adrenergic drugs?
- Used to treat heart failure and cardiac arrest
- Increase blood pressure
- Increase total peripheral resistance
- Cause vasconstriction of salivary glands, leads to xerostomia
What are anti-adrenergic drugs?
Beta adrenergic agonists
- Antihypertensives
- Reduce blood pressure
- Side effect: block adrenergic receptors on the mucous acini leading to reduced protein synthesis, quality of mucous saliva reduced
When are adrenergic drugs used in dentistry?
Beta adrenergic antagonists
Added to LA to prolong the action of the anaesthetic, reduce the risk of systemic toxicity as it has vasoconstrictive actions, helps to create a dry field.
